1. Field of the Invention
The invention relates to an apparatus and method for producing particles. The invention also relates to an apparatus and method for producing a molecular membrane.
2. Description of the Related Art
Vesicles, one kind of particles, have characteristics such as cell-like function as well as sequestration, preservation, concealment, and sustained release of substances, and have been widely used in technical fields such as biological fields, pharmaceutics (DDS, gene-introduction vectors, artificial erythrocyte), food, cosmetics, painting materials, environments, biosensors, and bioreactors. There are innumerable kinds of vesicles. Vesicles produced using 50% or more of a lipid as an emulsifier are classified in liposome. Further, being obtained by suspending an emulsifier or amphipatic molecules in a water-based medium, vesicles like a closed cytoplasmic membrane having a double structure observed in a biological membrane are classified in unilamellar vesicles (unilamellar vesicles or monolamellar vesicles), and vesicles like a closed cytoplasmic membrane having no less than triple structure are classified in multilamellar vesicles. The aqueous phase in the multilamellar vesicles contain a single aqueous phase or a plurality of aqueous phase.
Further, depending on the particle sizes and structures, the vesicles are classified into large multilamellar vesicles (MLV), small unilamellar vesicles (SUV), large unilamellar vesicles (LUV), and giant vesicles. The MLV is produced by a thin film formation method; the SUV is produced by an ultrasonic method and surfactant treatment method; the LUV is produced by a reverse-phase evaporation method, a solvent injection method, a French press method, a coacervation method, or a microcapsule method (S. Matsumoto, M. Kohda, and S. Murata, J. Coll. Interface Sci., 62: 147 [1977]; and S. Kim and G. M. Martin, Biocihmica et Biophysia Acta, 646: 1 [1981]); and the giant vesicle is produced by an electro-formation method (M. I. Angelova, S. Soleau, Ph. Meleard, J. F. Faucon, and P. Bothorel, Progr Colloid Polym Sci., 89: 127 [1992]; and P. Bucher, A. Fischer, P. L. Luisi, T. Oberholzer, and P. Walde, Langmuir, 14, 2712 [1998]). The particle sizes of the MLV, SUV, LUV, and giant vesicles produced by the above-mentioned methods are in ranges of 0.4 to 3.5 μm, 0.025 to 0.05 μm, 0.03 to 9 μm, and 50 to 100 μm, respectively.
To produce vesicles exhibiting little inconsistency in particle size by the above methods for producing vesicles, a series of complicated states such as drying and stirring lipid, voltage application, evaporation, ultrasonic wave, pressing, centrifugation, gel filtration separation, and dialysis are required, and it takes a long time (from several hours to a week or more) for the production. In addition, to enclose a substance in the produced vesicles, sealing steps by an electric shock method, an injection method by micro-capillary, an electropolation method, or a calcium fusion method, and thus, the steps are considerably complicated. Further, in the above-mentioned sealing steps, the sealing efficiency of a substance in vesicles is very low. Furthermore, since the production conditions are very severe, it is impossible to directly seal a physiologically active substance. Moreover, it is needed to remove the substance which is not enclosed. Additionally, since lipid is hydrolyzed by water in the case of the unilamellar vesicles formed in an aqueous solution, long term preservation of the unilamellar vesicles is impossible. Specifically, although it is generally possible to preserve the unilamellar vesicles for at longest 5 to 7 days in cool storage (4° C.), it is desirable to use them within 24 hours.
Comprehensively, it is difficult to produce vesicles enclosing a physiologically active substance by a conventional automatic method for producing vesicles having particle sizes of a narrow range. Furthermore, since the particle sizes of the produced vesicles are small, it is impossible to enclose a large quantity of polymers such as protein, DNA, or RNA in highly active state per unit volume of the vesicles.
Vesicles are required to be available promptly at a time of being needed in a needed amount. Further, in the case of using vesicles as a drug delivery system (DDS), it is needed to control the particle diameter and thickness of vesicles in terms of control of the administration dose of the drug, control of the sustained release of the drug, and control of the absorption of the drug, and it is desired to supply vesicles having excellent stability and high drug enclosing ratio. Further, a method of administration of the drug depends on the particle size of vesicles. Specifically, in general, vesicles having a diameter of 1 to 20 μm are administered by intravenous injection, vesicles having a diameter of 50 to 300 μm are administered by intra-arterial injection, and vesicles having a diameter of 300 μm or greater are administered by abdominal injection or oral administration. As a result, it is indispensable to control the particle sizes of vesicles. However, presently, no method for simply and quickly producing vesicles having uniform particle sizes, high physiological activity, and high substance enclosing ratio has been made available.
Further, a molecular membrane as one aspect of vesicles is very useful in fields such as a biosensor, a bioreactor, medical care, extraction, and environmental assessment. A technique of forming a molecular membrane in a micro-channel has been already proposed (JP-A 2005-185972 [KOKAI]). It is desired to provide a production kit for a molecular membrane, besides the molecular membrane formation method. Specifically, it has been desired to provide a detachable, disposable, and compact production kit for a molecular membrane, which is usable for in-situ analysis and simple analysis, that is, a molecular membrane production kit which can produce a molecular membrane having a three-dimensional structure exhibiting little inconsistency in size and shape.